Metal colloid particles with an average particle diameter of 1-100 nm are used in a number of functional materials because of small particle diameter and large surface area. When added to water, however, such particles easily aggregate due to a strong interparticle force. It is difficult to uniformly disperse the metal colloid particles. In addition, to stably disperse metal colloid particles, the pH of the solution must be controlled in a specific range. The applicable pH range is unduly limited (Patent Document 1).
A membrane integrity test method using substitute particles in a virus removal membrane has been disclosed. The integrity test is a test for confirming performance of virus removal membranes for removing viruses from solutions containing proteins, physiological active products, and the like after use (or occasionally before use). The integrity test methods include (1) a bubble pointing method, (2) a method of measuring the proportion of large pores in a pore diameter distribution of the membrane (for example, a method of using a low liquid-liquid interfacial tension), and (3) a method of filtering viral substitute particles. Of these methods, the method of filtering viral substitute particles is highly reliable since the principle of the method is particle sieving filtration which is the same as virus removal and, therefore, can obtain correlation of characteristics of the same type of mechanisms as virus removal. Particularly, there is an excellent correlation between removability of a gold colloid, used as viral substitute particles, by filtration and the virus removal capability of a membrane. In the integrity test, the membrane needs to be washed after use as a virus removal membrane to reduce the amount of residue in the membrane to the maximum extent possible. A solution such as an alkaline solution may be used as washing agent. Since a conventional gold colloid solution with only a limited pH range could be used, post-washing for strict control of the pH of the membrane after washing with washing agent was necessary. The operation was very complicated (Patent Document 2, Non-patent Document 1).
In the integrity test of a virus removal membrane for removing small viruses with a diameter of 20-25 nm such as parvovirus, even substitute for viral particles having correlation with virus removal capability has not existed. To exhibit characteristics of both consistent high removability of small viruses and high protein permeability, the membrane must have a special structure. The integrity test for the virus removal membrane having such a membrane structure must detect a very small difference in pore diameters. There have been no metal colloid solutions usable for such a purpose to date (Patent Document 3).    (Patent Document 1) JP-A-08-141388    (Patent Document 2) JP-A-07-132215    (Patent Document 3) WO 01/014047    (Non-patent document 1) Hiroki Murakami (Etd.), Animal Cell Technology; Basic & Applied Aspects, Netherland, Kluwer Academic Publishers, Vol. 4, 1992, p.87-102